Trifluoroacetic acid methylene chloride → (S)-4-(4-aminophenylthio)-3-(7-isopropylquinazolin-4-ylamino)-N-(1-phenylethyl)benzamide

HRID 605385Notes

Reaction equation

HRID 605385 reaction equation
[CH:1]([C:4]1[CH:13]=[C:12]2[C:7]([C:8]([NH:14][C:15]3[CH:20]=[C:19]([C:21](=[O:31])[NH:22][C@H:23]([C:25]4[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=4)[CH3:24])[CH:18]=[CH:17][C:16]=3[S:32][C:33]3[CH:38]=[CH:37][C:36]([NH:39]C(=O)OC(C)(C)C)=[CH:35][CH:34]=3)=[N:9][CH:10]=[N:11]2)=[CH:6][CH:5]=1)([CH3:3])[CH3:2].C(Cl)Cl.FC(F)(F)C(O)=O>>[NH2:39][C:36]1[CH:35]=[CH:34][C:33]([S:32][C:16]2[CH:17]=[CH:18][C:19]([C:21]([NH:22][C@H:23]([C:25]3[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=3)[CH3:24])=[O:31])=[CH:20][C:15]=2[NH:14][C:8]2[C:7]3[C:12](=[CH:13][C:4]([CH:1]([CH3:3])[CH3:2])=[CH:5][CH:6]=3)[N:11]=[CH:10][N:9]=2)=[CH:38][CH:37]=1

Participants

3

Reactant 2

HCID 21863450Trifluoroacetic acid methylene chlorideHCID 67040887(S)-tert-butyl 4-(2-(7-isopropylquinazolin-4-ylamino)-4-(1-phenylethylcarbamoyl)phenylthio)phenylcarbamate

Product 1

HCID 67040746(S)-4-(4-aminophenylthio)-3-(7-isopropylquinazolin-4-ylamino)-N-(1-phenylethyl)benzamideYield 73%

Procedure

The product of Example 431G (36 mg, 0.0568 mmol) was treated with 1:1 v/v methylene chloride/trifluoroacetic acid (3 mL) at room temperature for one hour then concentrated by rotary evaporation. The residue was dissolved in ethyl acetate (50 mL), washed with saturated aqueous sodium hydrogencarbonate (25 mL), water (25 mL), and brine (25 mL) then dried over magnesium sulfate, filtered, and concentrated by rotary evaporation. Purification by silica gel flash chromatography eluting with 3:97 methanol/methylene chloride afforded the title compound as a white solid (22 mg, 0.0412 mmol, 73%). 1H NMR (300 MHz, DMSO-D6) δ ppm 1.31 (d, J=6.99 Hz, 6 H) 1.45 (d, J=7.35 Hz, 3 H) 3.01-3.20 (m, 1 H) 5.07-5.26 (m, 1 H) 5.57 (s, 2 H) 6.61 (d, J=8.46 Hz, 2 H) 6.83 (d, J=8.46 Hz, 1H) 7.11 (d, J=8.82 Hz, 2 H) 7.17-7.43 (m, 5 H) 7.54-7.64 (m, 2 H) 7.69 (dd, J=8.46, 1.10 Hz, 1 H) 7.89 (d, J=1.47 Hz, 1 H) 8.43 (t, J=4.23 Hz, 2 H) 8.74 (d, J=7.72 Hz, 1 H) 9.88 (s, 1 H); MS (ESI+) m/z 534 (M+H)+, 1067 (2M+H); MS (ESI−) m/z 532 (M−H)−.

Workup

  1. concentrationthen concentrated by rotary evaporation
  2. dissolutionThe residue was dissolved in ethyl acetate (50 mL)
  3. washwashed with saturated aqueous sodium hydrogencarbonate (25 mL), water (25 mL), and brine (25 mL)
  4. dry with materialthen dried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated by rotary evaporation
  7. customPurification by silica gel flash chromatography
  8. washeluting with 3:97 methanol/methylene chloride

Sources & evidence

ORD record
ord-6befc63e1cb84276ae6e45638ccaedf9
Source dataset
uspto-grants-2011_03
Patent number
US07910595B2

Reaction notes

Loading…